Rondeau 2020.

Study characteristics
Methods	Study design: single‐arm study Country: multicentre (North America, Europe, Australia, Asia) Recruitment: not reported Intention to treat: safety analysis was conducted based upon intention to treat, however all other analyses were based upon only those with confirmed eligibility Follow‐up: 26 weeks with optional 4.5‐year extension period
Participants	Total number: enrolled (58); safety analysis (56); all other analyses (56) Age range: ≥ 18 years Inclusion criteria: ≥18 years; weight ≥ 40 kg; evidence of TMA (platelet count < 150 x 10³/µL; LDH ≥ 1.5 times the upper limit of normal range);SCr ≥ upper limit of normal range at screening; among patients with onset of TMA postpartum, persistent evidence of TMA for > 3 days after the day of childbirth; vaccinated against Neisseria meningitides or treated with appropriate prophylactic antibiotics until 2 weeks after meningococcal vaccination; if previous kidney transplantation: 1) known history of aHUS prior to current kidney transplant, or 2) no known history of aHUS, and persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen (e.g. suspending or reducing the dose) of CNI or mTORi Exclusion criteria: ADAMTS13 activity at or below 5% in plasma; evidence of STEC infection; evidence of S. pneumoniae infection; prior eculizumab exposure; receiving immunosuppression unless they were part of an established post‐transplant antirejection regimen, the patient had confirmed anticomplement antibodies, or if steroids were being used for a different condition; receiving PE/PI for a period of 28 days or longer before screening; receiving chronic dialysis at screening (defined as dialysis on a regular basis for ESKD)
Interventions	Intervention group Ravulizumab therapy: IV loading dose of 2400 mg, 2700 mg, and 3000 mg administered in patients at least 40 to < 60 kg, at least 60 to < 100 kg, and 100 kg or more, respectively, on day 1 and maintenance doses of 3000 mg, 3300 mg, and 3600 mg, respectively, on day 15, and then every 8 weeks thereafter
Outcomes	Primary outcomes Complete TMA response: defined as platelet count normalisation (≥ 150 x 109/L), LDH normalisation (< 246 U/L), and 25% or better improvement in SCr from baseline at 2 separate assessments obtained at least 28 days apart, and at any measurement in between Secondary outcomes Requirement for dialysis Time to complete TMA response Change in eGFR eGFR category (as evaluated by eGFR at select target days) Change in haematologic variables (platelets, LDH, Hb) Change in QoL (as measured by the Functional Assessment of Chronic Illness Therapy–Fatigue version 4)
Notes	Study sponsored by Alexian Pharmaceuticals, the manufacturer of ravulizumab
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	All subjects treated with ravulizumab. Given the rarity of the condition it is likely that all eligible participants encountered during the recruitment period were recruited, but this is not specifically reported. There is no reporting of how participants were selected for the study. Eligibility criteria clearly described.
Allocation concealment (selection bias)	High risk	Not randomised
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Very little missing outcome data
Selective reporting (reporting bias)	Low risk	All expected outcomes published
Other bias	Low risk	See below for single‐arm study bias assessment
Lead time bias / immortal time bias	Low risk	The time between first disease symptom and initiation of therapy was minimal (median 0.28 months)
Confounding by indication	Low risk	Given the rarity of the condition participants at all stages of the disease were included with similar prognostic factors as compared with other studies
Misclassification bias / information bias	Low risk	Clear dosing regimen and outcome reporting
Bias from natural recovery / regression to the mean	Low risk	Given the severe nature of the condition and historical data it is unlikely that there was no significant bias from natural recovery observed
Bias due to adjunctive therapies	Low risk	Plasma therapy (the main adjunctive treatment used in the other included studies) was not permitted in this study

CKD ‐ chronic kidney disease; CNI ‐ calcineurin inhibitor; ESKD ‐ end‐stage kidney disease; (e)GFR ‐ (estimated) glomerular filtration rate; (a)HUS ‐ (atypical) haemolytic uraemic syndrome; Hb ‐ haemoglobin; HRQoL ‐ health‐related QoL; IV ‐ intravenous/ly; LDH ‐ lactate dehydrogenase; mTORi ‐ mammalian target of rapamycin inhibitor; QoL ‐ quality of life; PCR ‐ protein:creatinine ratio; PE/PI ‐ plasma exchange/plasma infusion; RBC ‐ red blood cell; STEC ‐ Shiga toxin–producing E. coli infection; TMA ‐ thrombotic microangiopathy